Encoding precise movements in the rodent brain

我们的生存取决于我们如何通过学习过程来改变我们的行为，从而适应不断变化的环境。这种学习在大脑中被编码，作为神经回路执行的计算的变化，这反过来又驱动了行为。大脑的这一显著特性丰富了我们的行为技能，并定义了我们的身份。然而，关于学习是如何在大脑中编码的，还有很多东西有待理解。什么样的算法决定哪些突触、神经元和电路会对触发刺激做出反应？这种变化是如何储存的，又是如何导致行为学习的？ 为了回答这些问题，我们研究了一种相对简单且定义明确的行为，即小鼠小脑依赖性运动学习。小脑的神经元回路被很好地映射，小脑支持精确和校准良好的运动的学习，这可以在动物模型中以高度的精确度测量。由于小脑细胞结构相对简单，运动学习过程中感觉输入和运动输出之间发生的转换可以直接与行为结果联系起来。 我的研究计划的长期目标是确定记忆是如何编码的，在突触，细胞和电路水平。这项研究计划（短期目标）旨在使用一种简单而精确的视觉学习形式来确定学习在小脑突触和细胞中引起的变化。有三个具体目标： 1.确定前庭眼反射（VOR）学习的突触和细胞基质 2.确定VOR学习的结构特征。 3.为了揭示短期记忆如何转化为长期记忆 我们将利用电生理学，行为分析和形态学分析的组合，以确定如何VOR学习在小脑内编码。我们的主要重点是浦肯野细胞，以前的结果表明，这是记忆存储的网站。使用膜片钳记录，我们将测试什么样的变化是由学习引起的兴奋性和抑制性突触到浦肯野细胞。该分析将通过浦肯野细胞上突触的形状和密度变化的形态学分析来补充。此外，我们还将测试的假设，随着时间的推移，学习诱导的可塑性变化的网站从浦肯野细胞的输出脑干核。 这项研究计划将创造一个新的水平的理解复杂的计算，管理神经回路在学习过程中的适应。此外，拟议的研究将提供一个很好的培训机会，学员使用尖端的神经生理学技术，以确定突触和电路基础的学习行为。

Our survival depends on how well we adapt to changing conditions by modifying our behavior through a process of learning. Such learning is encoded in the brain, as changes in the computations performed by neural circuits, which in turn drives the behavior. This remarkable property of the brain enriches our behavioral repertoire and defines our identity. However, much remains to be understood about how learning is encoded in the brain. What algorithms determine which synapses, neurons, and circuits will change in response to triggering stimuli? How is such change stored, and how does this result in behavioral learning? We study a relatively simple and well-defined behavior, cerebellum-dependent motor learning in mice, in order to answer these questions. Cerebellar neuronal circuitry is well-mapped, and the cerebellum supports the learning of precise and well-calibrated movements, which can be measured with a high degree of precision in animal models. Because of the relative simplicity of cerebellar cytoarchitecture, the transformations that occur between sensory input and motor output during motor learning can be directly linked to a behavioral outcome. The long-term goals of my research program are to identify how memories are encoded, at the synaptic, cellular and circuit levels. This research proposal (short-term goals) aims to use a simple and precise form of oculomotor learning to determine what changes learning induces at synapses and cells in the cerebellum. There are three specific aims: 1. To identify the synaptic and cellular substrates of vestibulo-ocular reflex (VOR) learning 2. To determine the structural signatures of VOR learning. 3. To uncover how short-term memories are converted into long-term memories We will utilize a combination of electrophysiology, behavioral analysis and morphological analysis to identify how VOR learning is encoded within the cerebellum. Our primary focus is on the Purkinje cell, which previous results suggest is the site of memory storage. Using patch-clamp recordings, we will test what changes are induced by learning at excitatory and inhibitory synapses onto Purkinje cells. This analysis will be complemented by morphological analysis of changes in shape and density of synapses onto Purkinje cells. Furthermore, we will also test the hypothesis that, over time, the site of learning-induced plastic changes moves away from Purkinje cells to the output brainstem nuclei. This research program will create a new level of understanding of the complex computations that govern the adaptation of neural circuits during learning. Moreover, the proposed research will provide an excellent training opportunity for trainees to use cutting-edge neurophysiological techniques to identify the synaptic and circuit basis of learned behavior.